entecavir Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antivirals carbocyclic nucleosides 1019 142217-69-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • entecavir monohydrate
  • anhydrous entecavir
  • BMS-200475-01
  • entecavir
  • baraclude
  • entecavir hydrate
Entecavir, a guanosine nucleoside analogue with activity against HBV reverse transcriptase, is efficiently phosphorylated to the active triphosphate form, which has an intracellular half-life of 15 hours. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate functionally inhibits all three activities of the HBV reverse transcriptase: (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Entecavir triphosphate is a weak inhibitor of cellular DNA polymerases alpha, beta, and delta and mitochondrial DNA polymerase gamma with Ki values ranging from 18 to > 160 microM.
  • Molecular weight: 277.28
  • Formula: C12H15N5O3
  • CLOGP: -2.58
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 4
  • TPSA: 125.76
  • ALOGS: -1.63
  • ROTB: 2

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.50 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 2.40 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 70 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.05 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 99 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
March 29, 2005 FDA BRISTOL MYERS SQUIBB

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hepatitis B 206.21 19.68 50 4078 3842 53341096
Hepatitis B reactivation 165.82 19.68 37 4091 1971 53342967
Drug resistance 150.59 19.68 57 4071 19905 53325033
Hepatitis B DNA increased 114.40 19.68 19 4109 201 53344737
Viral load increased 99.21 19.68 23 4105 1452 53343486
Exposure via body fluid 79.60 19.68 16 4112 512 53344426
Hepatocellular carcinoma 68.88 19.68 20 4108 3060 53341878
Hypophosphataemia 65.82 19.68 25 4103 8780 53336158
Abortion induced 54.09 19.68 23 4105 10803 53334135
Hepatic cancer 53.67 19.68 17 4111 3484 53341454
Viral mutation identified 53.25 19.68 15 4113 2059 53342879
Pathogen resistance 43.23 19.68 17 4111 6543 53338395
Osteomalacia 42.07 19.68 10 4118 703 53344235
Liver transplant 41.94 19.68 13 4115 2481 53342457
Hepatic failure 39.62 19.68 28 4100 35778 53309160
Fanconi syndrome acquired 37.93 19.68 10 4118 1071 53343867
Hepatic function abnormal 34.35 19.68 26 4102 36873 53308065
Maternal exposure during pregnancy 33.40 19.68 50 4078 155589 53189349
Hepatic encephalopathy 29.10 19.68 15 4113 10844 53334094
Pregnancy on contraceptive 27.43 19.68 8 4120 1241 53343697
Febrile neutropenia 27.34 19.68 37 4091 104899 53240039
Neutrophil count decreased 25.96 19.68 25 4103 49073 53295865
Cryoglobulinaemia 23.84 19.68 6 4122 535 53344403
Platelet count decreased 23.55 19.68 35 4093 108064 53236874
Fanconi syndrome 23.36 19.68 7 4121 1193 53343745
Abortion spontaneous 23.26 19.68 23 4105 46612 53298326
Leukopenia 22.39 19.68 28 4100 73435 53271503
Viral uveitis 21.47 19.68 4 4124 85 53344853
Gastroenteritis staphylococcal 21.42 19.68 4 4124 86 53344852
Renal impairment 21.12 19.68 29 4099 83289 53261649
Electrocardiogram P pulmonale 20.03 19.68 3 4125 15 53344923

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hepatitis B 379.38 17.34 117 8689 6224 32498496
Drug resistance 318.92 17.34 145 8661 22820 32481900
Hepatocellular carcinoma 272.36 17.34 103 8703 10167 32494553
Hepatic cancer 264.48 17.34 92 8714 7148 32497572
Viral mutation identified 256.01 17.34 73 8733 2946 32501774
Hepatic failure 182.60 17.34 116 8690 35564 32469156
Genotype drug resistance test 182.11 17.34 29 8777 45 32504675
Hepatitis B reactivation 178.45 17.34 57 8749 3392 32501328
Hepatitis B DNA increased 177.33 17.34 39 8767 526 32504194
Pathogen resistance 119.18 17.34 56 8750 9454 32495266
Multiple-drug resistance 115.17 17.34 42 8764 3733 32500987
Osteomalacia 108.23 17.34 29 8777 924 32503796
Fanconi syndrome acquired 103.71 17.34 34 8772 2196 32502524
Viral load increased 99.65 17.34 36 8770 3114 32501606
Hepatic cirrhosis 99.45 17.34 60 8746 16749 32487971
Hepatic encephalopathy 95.50 17.34 56 8750 14839 32489881
Hypophosphataemia 95.25 17.34 47 8759 8828 32495892
Ascites 92.74 17.34 81 8725 40110 32464610
Blood HIV RNA decreased 86.58 17.34 12 8794 0 32504720
Hepatic function abnormal 72.09 17.34 74 8732 44766 32459954
Hepatitis B surface antigen positive 61.95 17.34 13 8793 138 32504582
Blood phosphorus decreased 60.21 17.34 25 8781 3141 32501579
Viral infection 52.75 17.34 40 8766 16210 32488510
Genotype drug resistance test positive 51.30 17.34 19 8787 1762 32502958
Osteoporosis 48.66 17.34 34 8772 12148 32492572
Portal vein thrombosis 40.72 17.34 20 8786 3715 32501005
Fanconi syndrome 40.19 17.34 16 8790 1804 32502916
Palmar-plantar erythrodysaesthesia syndrome 38.83 17.34 33 8773 15716 32489004
Alanine aminotransferase increased 37.25 17.34 72 8734 78407 32426313
Blood bilirubin increased 34.00 17.34 47 8759 38737 32465983
Renal impairment 32.72 17.34 75 8731 91897 32412823
Autoimmune haemolytic anaemia 32.18 17.34 18 8788 4356 32500364
Hypocalciuria 28.86 17.34 4 8802 0 32504720
Renal tubular injury 28.65 17.34 10 8796 781 32503939
Mycoplasma infection 28.05 17.34 8 8798 322 32504398
Portal vein occlusion 27.33 17.34 6 8800 80 32504640
Parotid gland haemorrhage 27.12 17.34 5 8801 25 32504695
Asymptomatic viral hepatitis 26.65 17.34 5 8801 28 32504692
Renal tubular acidosis 25.54 17.34 12 8794 2020 32502700
Retinopathy hypertensive 24.78 17.34 7 8799 272 32504448
Liver transplant 24.53 17.34 13 8793 2827 32501893
Malignant anorectal neoplasm 24.38 17.34 5 8801 47 32504673
Hepatitis B e antigen positive 23.83 17.34 5 8801 53 32504667
Aspartate aminotransferase increased 23.42 17.34 54 8752 66375 32438345
Foetal heart rate abnormal 22.73 17.34 6 8800 180 32504540
Foetal hypokinesia 21.97 17.34 7 8799 412 32504308
Blood uric acid 21.64 17.34 3 8803 0 32504720
Retinal toxicity 21.62 17.34 7 8799 434 32504286
Liver transplant rejection 21.59 17.34 11 8795 2208 32502512
Dyspnoea 21.49 17.34 41 8765 362004 32142716
Renal glycosuria 21.23 17.34 4 8802 23 32504697
Blood creatine phosphokinase increased 20.67 17.34 41 8765 45435 32459285
Antiviral drug level below therapeutic 19.57 17.34 3 8803 3 32504717
Alkalosis hypokalaemic 19.57 17.34 3 8803 3 32504717
Venoocclusive liver disease 19.32 17.34 16 8790 7349 32497371
Laryngeal erythema 18.35 17.34 3 8803 6 32504714
Jaundice 18.25 17.34 33 8773 34125 32470595
Lipase increased 18.06 17.34 17 8789 9240 32495480
Haemorrhagic cholecystitis 18.04 17.34 4 8802 56 32504664
Schistosomiasis 17.91 17.34 4 8802 58 32504662
Amylase increased 17.67 17.34 14 8792 6041 32498679
Hepatitis B antigen positive 17.49 17.34 3 8803 9 32504711

Pharmacologic Action:

SourceCodeDescription
ATC J05AF10 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Nucleoside and nucleotide reverse transcriptase inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
CHEBI has role CHEBI:36044 anti-virus drug
CHEBI has role CHEBI:59897 RNA-dependent DNA polymerase inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic type B viral hepatitis indication 61977001
Lamivudine-Refractory Chronic Hepatitis B indication
Lactic acidosis contraindication 91273001 DOID:3650
Liver function tests abnormal contraindication 166603001
Steatosis of liver contraindication 197321007
Impaired renal function disorder contraindication 197663003
Drug Resistance to Anti-retroviral Therapy contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.56 acidic
pKa2 12.33 acidic
pKa3 13.37 acidic
pKa4 4.58 Basic
pKa5 3.37 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Protein P Polyprotein INHIBITOR CHEMBL CHEMBL
Protein P Polyprotein WOMBAT-PK
Capsid protein Unclassified EC50 9.62 CHEMBL

External reference:

IDSource
4024911 VUID
N0000171606 NUI
D04008 KEGG_DRUG
4024911 VANDF
C0971023 UMLSCUI
CHEBI:473990 CHEBI
CHEMBL713 ChEMBL_ID
DB00442 DRUGBANK_ID
C413685 MESH_SUPPLEMENTAL_RECORD_UI
135398508 PUBCHEM_CID
209216-23-9 SECONDARY_CAS_RN
5968Y6H45M UNII
1546027 RXNORM
19722 MMSL
228280 MMSL
67562 MMSL
d05525 MMSL
010730 NDDF
416248007 SNOMEDCT_US
416644000 SNOMEDCT_US
725853008 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1611 TABLET, FILM COATED 0.50 mg ORAL NDA 28 sections
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1612 TABLET, FILM COATED 1 mg ORAL NDA 28 sections
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1614 SOLUTION 0.05 mg ORAL NDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 10135-615 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 10135-616 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 16714-717 TABLET, FILM COATED 0.50 mg ORAL ANDA 27 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 16714-718 TABLET, FILM COATED 1 mg ORAL ANDA 27 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 16729-388 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 16729-389 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42291-261 TABLET, FILM COATED 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42291-262 TABLET, FILM COATED 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42806-658 TABLET 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42806-659 TABLET 1 mg ORAL ANDA 28 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 50771-013 TABLET, FILM COATED 0.50 mg ORAL ANDA 28 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 50771-014 TABLET, FILM COATED 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51407-064 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51407-065 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51991-895 TABLET 0.50 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51991-896 TABLET 1 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60050-057 TABLET 0.50 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60050-077 TABLET 1 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60687-216 TABLET 0.50 mg ORAL ANDA 26 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 62227-101 TABLET 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 62227-102 TABLET 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 65162-446 TABLET, FILM COATED 0.50 mg ORAL ANDA 26 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 65162-449 TABLET, FILM COATED 1 mg ORAL ANDA 26 sections
Entecavir Human Prescription Drug Label 1 65862-841 TABLET 0.50 mg ORAL ANDA 26 sections
Entecavir Human Prescription Drug Label 1 65862-842 TABLET 1 mg ORAL ANDA 26 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 68382-920 TABLET, FILM COATED 0.50 mg ORAL ANDA 24 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 68382-921 TABLET, FILM COATED 1 mg ORAL ANDA 24 sections